PBS 803 Class 6 Antigen Recognition September 8

PBS 803 - Class #6 Antigen Recognition September 8 th, 2016 Suggested Reading: pages 79 -102 Individual molecules of human immunoglobulin G, the predominant antibody in blood and connective tissue. Fig. from Parham cover page for Chapter 4 Note: figures from Parham will reference the 3 rd edition

Learning Objectives for Class #6 part I · Describe the basic structure of immunoglobulins (Igs) and compare with the BCR (e. g. light & heavy chains, constant vs. variable regions, hinge, Fc, Fab) · Compare and contrast the structures and functions of Igs with T-cell receptors · Compare and contrast the antigen recognition by T and B lymphocytes, both in the types of antigens recognized, and the requirement of antigen-presenting cells. · Describe in general terms the structure of the TCR ( β and γδ TCRs), and at least one of the associated polypeptides of the TCR complex: CD 3. · Recall the overall chain structure (e. g. monomer, dimer, pentamer) of the major isotype classes of antibodies (e. g. Ig. A, Ig. D, Ig. E, Ig. G, Ig. M)

Learning Objectives for Class #6 part 2 · Compare affinity and avidity and describe their role in immune processes · Compare and contrast monoclonal and polyclonal antibodies · Describe and explain the molecular genetic mechanisms involved in the generation of antibody diversity (e. g. multiple V region gene elements, variable recombination, junctional diversity) · Explain allelic exclusion with respect to immunoglobulin gene expression ·Describe the role of the bone marrow in lymphocyte origin and B cell maturation · Compare different fates of T lymphocytes undergoing maturation in the thymus (e. g. positive selection, negative selection and death by neglect)

Comparison of surface immunoglobulin (the BCR), antibody and the TCR

Mechanisms by which antibodies combat infection

Properties of Antibodies, BCRs, and TCRs

Structure of antibodies

Binding of an antigen by an antibody

Variable regions of BCR and TCR produced by similar mechanisms Functionality of constant regions unaffected by diverse antigen recognition regions Doan Fig. 8. 4 and 8. 8

Major isotypes of antibodies

Affinity vs. Avidity Fig. 5. 13 Cellular and Molecular Immunology Abbas et. al.

Generation of monoclonal antibodies from hybridomas

Selected monoclonal antibodies in clinical use.

Polyclonal vs. Monoclonal antibodies

The T-cell receptor (TCR)

Antigen recognition by immunoglobulins and TCRs

The T-cell Receptor (TCR) left and TCR signaling complexes (right) of most T cell lymphocytes

Maturation of B and T lymphocytes cells that can not express functional receptor die by apoptosis

DNA recombination used in generation of both antibody and TCR diversity -referred to as somatic recombination since occurs in somatic cells, unlike recombination that occurs in germ cells during meiosis

DNA recombination used to generate antibody

Generation of diversity in antigen receptors Combinatorial diversity of differing segments encoding for variable regions, through DNA recombination Junctional diversity addition/removal of nucleotides

Production of mature (yet naïve) B cell -requires functional rearrangement of both one heavy and one light chain mature resting B cell will expresses transmembrane Ig. M and Ig. D

Allelic exclusion -allelic exclusion ensures that only one BCR is made per lymphocyte once functional light chain successfully made, expression of light chain from other chromosome shut off (similar process occurs for heavy chain) Doan Fig. 8. 1

Maturation and selection of MHC-restricted T lymphocytes -In addition to being required to express functional TCR to avoid apoptosis, developing T lymphocytes must also be able to weakly recognize MHC cells that don’t recognize MHC at all die by apoptosis end result are MHC restricted cells that are single positive (either CD 4+ or CD 8+, but not both)